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Disparities in sleep health are important but under-recognized contributors to health disparities. Understanding the factors contributing to sleep heath disparities and developing effective interventions are critical to improving all aspects of heath. Sleep heath disparities are impacted by socio-economic status, racism, discrimination, neighborhood segregation, geography, social patterns and access to healthcare as well as by cultural beliefs necessitating a cultural appropriateness component in any intervention devised for reducing sleep health disparities. Pediatric sleep disparities require innovative and urgent intervention to establish a foundation of lifelong healthy sleep. Tapping the vast potential of technology in improving sleep health access may be an underutilized tool to reduce sleep heath disparities. Identifying, implementing, replicating and disseminating successful interventions to address sleep disparities have the potential to reduce overall disparities in health and quality of life.

The therapeutic and toxic effects of drugs are often generated through effects on distinct cell types in the body. Selective delivery of drugs to specific cells or cell lineages would, therefore, have major advantages, in particular, the potential to significantly improve the therapeutic window of an agent. Cells of the monocyte-macrophage lineage represent an important target for many therapeutic agents because of their central involvement in a wide range of diseases including inflammation, cancer, atherosclerosis, and diabetes. We have developed a versatile chemistry platform that is designed to enhance the potency and delivery of small-molecule drugs to intracellular molecular targets. One facet of the technology involves the selective delivery of drugs to cells of the monocyte-macrophage lineage, using the intracellular carboxylesterase, human carboxylesterase-1 (hCE-1), which is expressed predominantly in these cells. Here, we demonstrate selective delivery of many types of intracellularly targeted small molecules to monocytes and macrophages by attaching a small esterase-sensitive chemical motif (ESM) that is selectively hydrolyzed within these cells to a charged, pharmacologically active drug. ESM versions of histone deacetylase (HDAC) inhibitors, for example, are extremely potent anticytokine and antiarthritic agents with a wider therapeutic window than conventional HDAC inhibitors. In human blood, effects on monocytes (hCE-1-positive) are seen at concentrations 1000-fold lower than those that affect other cell types (hCE-1-negative). Chemical conjugates of this type, by limiting effects on other cells, could find widespread applicability in the treatment of human diseases where monocyte-macrophages play a key role in disease pathology.